Activation of Glial FGFRs Is Essential in Glial Migration, Proliferation, and Survival and in Glia-Neuron Signaling during Olfactory System Development

Development of the adult olfactory system of the moth Manduca sexta depends on reciprocal interactions between olfactory receptor neuron (ORN) axons growing in from the periphery and centrally-derived glial cells. Early-arriving ORN axons induce a subset of glial cells to proliferate and migrate to form an axon-sorting zone, in which later-arriving ORN axons will change their axonal neighbors and change their direction of outgrowth in order to travel with like axons to their target areas in the olfactory (antennal) lobe. These newly fasciculated axon bundles will terminate in protoglomeruli, the formation of which induces other glial cells to migrate to surround them. Glial cells do not migrate unless ORN axons are present, axons fail to fasciculate and target correctly without sufficient glial cells, and protoglomeruli are not maintained without a glial surround. We have shown previously that Epidermal Growth Factor receptors and the IgCAMs Neuroglian and Fasciclin II play a role in the ORN responses to glial cells. In the present work, we present evidence for the importance of glial Fibroblast Growth Factor receptors in glial migration, proliferation, and survival in this developing pathway. We also report changes in growth patterns of ORN axons and of the dendrites of olfactory (antennal lobe) neurons following blockade of glial FGFR activation that suggest that glial FGFR activation is important in reciprocal communication between neurons and glial cells

Roles of Specific Membrane Lipid Domains in EGF Receptor Activation and Cell Adhesion Molecule Stabilization in a Developing Olfactory System

BACKGROUND:Reciprocal interactions between glial cells and olfactory receptor neurons (ORNs) cause ORN axons entering the brain to sort, to fasciculate into bundles destined for specific glomeruli, and to form stable protoglomeruli in the developing olfactory system of an experimentally advantageous animal species, the moth Manduca sexta. Epidermal growth factor receptors (EGFRs) and the cell adhesion molecules (IgCAMs) neuroglian and fasciclin II are known to be important players in these processes. METHODOLOGY/PRINCIPAL FINDINGS:We report in situ and cell-culture studies that suggest a role for glycosphingolipid-rich membrane subdomains in neuron-glia interactions. Disruption of these subdomains by the use of methyl-beta-cyclodextrin results in loss of EGFR activation, depletion of fasciclin II in ORN axons, and loss of neuroglian stabilization in the membrane. At the cellular level, disruption leads to aberrant ORN axon trajectories, small antennal lobes, abnormal arrays of olfactory glomerul, and loss of normal glial cell migration. CONCLUSIONS/SIGNIFICANCE:We propose that glycosphingolipid-rich membrane subdomains (possible membrane rafts or platforms) are essential for IgCAM-mediated EGFR activation and for anchoring of neuroglian to the cytoskeleton, both required for normal extension and sorting of ORN axons

An NADPH-Dependent Genetic Switch Regulates Plant Infection by the Rice Blast Fungus

To cause rice blast disease, the fungus Magnaporthe oryzae breaches the tough outer cuticle of the rice leaf by using specialized infection structures called appressoria. These cells allow the fungus to invade the host plant and proliferate rapidly within leaf tissue. Here, we show that a unique NADPH-dependent genetic switch regulates plant infection in response to the changing nutritional and redox conditions encountered by the pathogen. The biosynthetic enzyme trehalose-6-phosphate synthase (Tps1) integrates control of glucose-6-phosphate metabolism and nitrogen source utilization by regulating the oxidative pentose phosphate pathway, the generation of NADPH, and the activity of nitrate reductase. We report that Tps1 directly binds to NADPH and, thereby, regulates a set of related transcriptional corepressors, comprising three proteins, Nmr1, Nmr2, and Nmr3, which can each bind NADP. Targeted deletion of any of the Nmr-encoding genes partially suppresses the nonpathogenic phenotype of a Δtps1 mutant. Tps1-dependentNmr corepressors control the expression of a set of virulence-associated genes that are derepressed during appressorium-mediated plant infection. When considered together, these results suggest that initiation of rice blast disease by M. oryzae requires a regulatory mechanism involving an NADPH sensor protein, Tps1, a set of NADP-dependent transcriptional corepressors, and the nonconsuming interconversion ofNADPHandNADPacting as signal transducer

Effects of emergency department Care Coordination Team referrals in older people presenting with a fall

Objectives: The study aims to describe the characteristics of patients presenting to an ED with a fall and evaluate multidisciplinary Care Coordination Team (CCT) referrals on patient outcomes. Methods: A single-centred retrospective analysis of electronic data at an adult tertiary hospital was performed using data from 2004 to 2009 of presentations for patients aged 65 years or over with a fall. The primary outcome measure was representation to hospital within 30 days, comparing patients referred to CCT and those not referred. Secondary outcomes were differences in demographic characteristics, mode of arrival, triage score and readmission. Results: The proportion of ED patients presenting with a fall and their mean age is stable over time. From 2006 to 2009, 5162 fallers were referred to CCT in a decreasing trend, but with increased urgency. Statistically significant predictors for being referred to CCT were increasing age, being female, arriving by ambulance, being transferred from a nursing home and higher socioeconomic category. Arrival by ambulance and a history of previous falls were associated with representation and readmission. A decreasing trend from 2006 to 2009 was seen in rate ratios and odds ratios via regression modelling for both representation and readmission in patients referred to CCT. Conclusion: Maturing of the CCT is associated with a decrease in representation and readmission rate. Over time, the CCT attended higher urgency patients associated with stable admission rates. These associations were not significant and the clinical effectiveness of ED CCTs requires further examination

PAID TO PUMP: How a tax credit could discourage conservation of the High Plains Aquifer

In 1965’s United States v. Shurbet case, an irrigator from Texas asserted his claim for a depletion tax deduction for groundwater pumped from the High Plains Aquifer. He argued that the unique conditions of the southern High Plains region - a plateau where the shallow aquifer is recharged only through precipitation at a slow rate - meant the groundwater resource would be depleted in time. The state argued that groundwater was not fundamentally an exhaustible natural deposit, but the Supreme Court concluded the tax deduction was appropriate given the “peculiar” conditions in the area. It was stated the decision was not meant to establish a precedent regarding cost depletion of groundwater. The findings of the Shurbet case were intended to be limited to the southern High Plains region. However, in a 1980 lawsuit against the IRS, the Gigot brothers of Kansas sought to expand the deduction to allow depletion of the aquifer beneath their 30,000 acre farm in Kansas. The case was settled in the district court with a ruling allowing the brothers’ deductions to continue, thereby extending the Shurbet decision to include all landowners extracting from the approximately 174,000 square miles of land overlying the High Plains Aquifer. Currently, the estimated value of the credit is highest in parts of northern Texas, eastern Colorado, western Kansas, and south central Nebraska

Two TIR-like domain containing proteins in a newly emerging zoonotic Staphylococcus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response

Staphylococcus aureus, sequence type (ST) 398, is an emerging pathogen and the leading cause of livestock-associated methicillin-resistant Staphylococcus aureus infections in Europe and North America. This strain is characterised by high promiscuity in terms of host species and also lacks several traditional S. aureus virulence factors. This does not however explain the apparent ease with which it crosses species-barriers. Recently, TIR-domain containing proteins (Tcps) inhibitng the innate immune response were identified in some Gram-negative bacteria. Here we report the presence of two proteins, S. aureus TIR-like Protein 1 (SaTlp1) and S. aureus TIR-like Protein 2 (SaTlp2), expressed by ST398 which contain Domain of Unknown Function 1863 (DUF1863), similar to the Toll/IL-1 receptor (TIR) domain. In contrast to the Tcps in Gram-negative bacteria, our data suggest that SaTlp1 and SaTlp2 increase activation of the transcription factor NF-κB as well as downstream pro-inflammatory cytokines and immune effectors. To assess the role of both proteins as potential virulence factors knock-out mutants were created. These showed the potential for a slightly increased survival rate in a murine infectious model compared to the wild-type strain at one dose, but the data did not reach level of significance. Our data suggest that both proteins may act as factors contributing to the enhanced ability of ST398 to cross species-barriers

The Amateur Sky Survey Mark III Project

The Amateur Sky Survey (TASS) is a loose confederation of amateur and professional astronomers. We describe the design and construction of our Mark III system, a set of wide-field drift-scan CCD cameras which monitor the celestial equator down to thirteenth magnitude in several passbands. We explain the methods by which images are gathered, processed, and reduced into lists of stellar positions and magnitudes. Over the period October, 1996, to November, 1998, we compiled a large database of photometric measurements. One of our results is the "tenxcat" catalog, which contains measurements on the standard Johnson-Cousins system for 367,241 stars; it contains links to the light curves of these stars as well.Comment: 20 pages, including 4 figures; additional JPEG files for Figures 1, 2. Submitted to PAS

Compact HI clouds from the GALFA-HI survey

The Galactic Arecibo L-band Feed Array HI (GALFA-HI) survey is mapping the entire Arecibo sky at 21-cm, over a velocity range of -700 to +700 km/s (LSR), at a velocity resolution of 0.18 km/s and a spatial resolution of 3.5 arcmin. The unprecedented resolution and sensitivity of the GALFA-HI survey have resulted in the detection of numerous isolated, very compact HI clouds at low Galactic velocities, which are distinctly separated from the HI disk emission. In the limited area of ~4600 deg$^2$ surveyed so far, we have detected 96 of such compact clouds. The detected clouds are cold with a median T$_{k,max}$ (the kinetic temperature in the case in which there is no non-thermal broadening) of 300 K. Moreover, these clouds are quite compact and faint, with median values of 5 arcmin in angular size, 0.75 K in peak brightness temperature, and $5 \times 10^{18}$ cm$^{-2}$ in HI column density. Most of the clouds deviate from Galactic rotation at the 20-30 km/s level, and a significant fraction show evidence for a multiphase medium and velocity gradients. No counterparts for these clouds were found in other wavebands. From the modeling of spatial and velocity distributions of the whole compact cloud population, we find that the bulk of the compact clouds are related to the Galactic disk, and their distances are likely to be in the range of 0.1 to a few kpc. We discuss various possible scenarios for the formation and maintenance of this cloud population and its significance for Galactic ISM studies.Comment: Accepted for publication in the Astrophysical Journa

Clinical Study of Ursodeoxycholic Acid in Barrett's Esophagus Patients

Prior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett’s esophagus (BE) and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with BE. Twenty-nine BE patients received UDCA treatment at a daily dose of 13–15 mg/kg/day for six months. The clinical activity of UDCA was assessed by evaluating changes in gastric bile acid composition and markers of oxidative DNA damage (8-hydroxydeoxyguanosine, 8OHdG), cell proliferation (Ki67), and apoptosis (cleaved caspase 3, CC3) in BE epithelium. The bile acid concentrations in gastric fluid were measured by liquid chromatography-mass spectrometry. At baseline, UDCA (sum of unchanged and glycine/taurine conjugates) accounted for 18.2% of total gastric bile acids. Post UDCA intervention, UDCA increased significantly to account for 93.39% of total gastric bile acids (p<0.0001). The expression of markers of oxidative DNA damage, cell proliferation, and apoptosis was assessed in the BE biopsies by immunohistochemistry. The selected tissue biomarkers were unchanged after 6 months of UDCA intervention. We conclude that high dose UDCA supplementation for six months resulted in favorable changes in gastric bile acid composition but did not modulate selected markers of oxidative DNA damage, cell proliferation, and apoptosis in the BE epithelium